Noninvasive determination of exercise cardiac function following Fontan operation.
The purpose of this investigation was to define mechanisms which increase cardiac output during exercise in patients without a functioning right ventricle. Radionuclide studies were performed at rest and during upright bicycle exercise on 16 patients following Fontan procedures and compared to studies in 10 normal children. The mean cardiac index of patients following Fontan procedures was 5.2 +/- 2.0 L/min/m2 (standard deviation) at rest and increased to 9.4 +/- 3.5 L/min/m2 during exercise (p less than 0.0001). Exercise values were similar to those observed in normal children. The mechanisms utilized to achieve high cardiac output following Fontan procedures included an increase in heart rate. Mean systemic ventricular ejection fractions were significantly less than in normal children. The resting ventricular end-diastolic volume and stroke volume indices were above normal and remained constant during exercise to high heart rates. These data clearly document that a large exercise cardiac output can be achieved by patients without a functioning right ventricle.


Molecular Beacon Gold Nanosensors for Leucine-Rich Alpha-2-Glycoprotein-1 Detection in Pathological Angiogenesis.
Leucine-rich alpha-2-glycoprotein-1 (Lrg1) is an emerging biomarker for angiogenesis. Its expression in ocular tissues is up-regulated in both human patients with proliferative diabetic retinopathy and rodent models of pathological angiogenesis. However, there is no existing sensor that allows visualization and monitoring of Lrg1 expression noninvasively and in real time. Herein, we report a nucleic acid-gold nanorod-based nanosensor for the noninvasive monitoring of cellular Lrg1 expression in angiogenesis. Specifically, this platform is constructed by covalently conjugating molecular beacons onto gold nanorods, which prequench the fluorophores on the molecular beacons. Upon intracellular entry and endosomal escape, the complexes interact with cellular Lrg1 mRNA through hybridization of the loop area of the molecular beacons. This complexation distances the fluorophores from nanorod and restores the prequenched fluorescence. The reliability of this platform is confirmed by examining the increased Lrg1 expression in migrating keratinocytes and the Lrg1 gene changes in different postnatal stages of mouse retinal vasculature growth in the mouse retina model.


Impact of kidney size on the outcome of diabetic patients receiving hemodialysis.
Diabetic patients normally have enlarged or normal-sized kidneys throughout their lifetime, but some diabetic uremic patients have small kidneys. It is uncertain if kidney size could have any negative impact on outcome in hemodialysis patients. This longitudinal, observational cohort study recruited 301 diabetic hemodialysis patients in 2015, and followed until 2019. Patients were stratified into two subgroups according to their kidney sizes before dialysis, as small (n = 32) or enlarged or normal (n = 269). Baseline demographic, hematological, biochemical, nutritional, inflammatory and dialysis related data were collected for analysis. Patients with small kidney size were not only older (P<0.001) and had lower body mass index (P = 0.016), but had also higher blood uric acid concentration (P<0.001) compared with patients with enlarged or normal kidney size. All patients received adequate doses of hemodialysis since the Kt/V and urea reduction ratio was 1.7±0.3 and 0.7±0.1, respectively. Patients with small size kidneys received higher erythropoietin dose than patients with enlarged or normal kidney size (P = 0.031). At the end of analysis, 92 (30.6%) patients expired. Kaplan-Meier analysis revealed no survival difference between both groups (P = 0.753). In a multivariate logistic regression model, it was demonstrated that age (P<0.001), dialysis duration (P<0.001), as well as blood albumin (P = 0.012) and low-density lipoprotein (P = 0.009) concentrations were significantly correlated with mortality. Small kidney size on starting hemodialysis was not related with an augmented risk for death in diabetic patients receiving hemodialysis. Further studies are necessary.


Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching Sessions.
Although urine microscopy is an important step in the initial evaluation of a patient with kidney disease, internal medicine residents have minimal exposure to this technique during their training. The goal of this study was to understand knowledge of and attitudes toward urine microscopy among internal medicine residents and to implement virtual urine microscopy teaching sessions. A voluntary, anonymous, online survey was sent to all of the categorical internal medicine residents (n=131) training at the Icahn School of Medicine at Mount Sinai (ISMMS). The survey included 13 questions to assess attitudes toward, experience with, and clinical interpretation of urine microscopy specimens. In response to the survey results, we implemented virtual urine microscopy teaching sessions using video conferencing software that incorporated real-time urine sediment analysis with nephrology fellows and attending nephrologists. The survey response rate was 45% (59 of 131). Forty-seven percent (28 of 59) of respondents reported performing urine microscopy at least once during their training, and 75% (44 of 59) of respondents did not feel comfortable performing urine microscopy. The majority of residents (92%; 54 of 59) reported they felt urine microscopy was very helpful or somewhat helpful in the evaluation of patients with AKI. Overall, 41% of responses to clinical interpretation questions were considered correct. Following survey completion, virtual urine microscopy sessions were held monthly and well received by the participants. Our study found that internal medicine residents perceive urine microscopy as a helpful diagnostic tool, although lack the skills to perform and interpret urine microscopy sediments. Virtual educational sessions using video conferencing software are a technically feasible approach to teaching urine microscopy to internal medicine residents. Future studies include a study of the effect of these sessions on learning of urine microscopy. This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2021_01_28_KID0006282020.mp3.


How somatosensory evoked potentials improve the diagnosis of the disturbance of consciousness: A retrospective analysis.
The interpeak latency is a crucial characteristic of upper limb somatosensory evoked potentials (USEPs). However, the existing research on the correlation between interpeak latency and consciousness disorders is currently limited. We aimed to investigate how USEPs can contribute to the diagnosis of consciousness disorders. A retrospective analysis was conducted on 10 patients who underwent repetitive transcranial magnetic stimulation (rTMS) for consciousness disorders. The interpeak latency N13-N20, Glasgow coma scale (GCS), and Chinese Nanjing persistent vegetative state scale (CNPVSS) were evaluated before and after rTMS treatment, and the linear correlation between N13-N20, GCS, and CNPVSS was analysed. The scores of CNPVSS and GCS significantly increased in the first, second, and third months after rTMS. The N13-N20 was shorter in the second and third months after rTMS compared to before treatment. rTMS was found to shorten the N13-N20 latency, and there was a negative correlation between N13-N20 and the score of consciousness disorders. N13-N20 can serve as an objective index for evaluating consciousness disorders. This research provides potential insights for doctors in diagnosing patients with consciousness disorders.


On the effects of weak bases and monensin on sorting and processing of lysosomal enzymes in human cells.
The weak bases chloroquine, primaquine, NH4Cl and the ionophore monensin exert similar but not identical effects on sorting, transport and processing of cathepsin D in several human cell lines (fibroblasts, HepG2 cells, U937, monocytes). The drugs inhibit the segregation of newly synthesized cathepsin D from the secretory route. The kinetics of transport of nonsegregated cathepsin D precursor along the secretory route is retarded resulting in a delayed hypersecretion. Higher concentrations of the drugs can arrest the intracellular transport completely. The extent of inhibition of segregation varies among the different human cell types tested. Thus, in fibroblasts the secretion can be stimulated to exceed 80%, while in U937 cells the secretion cannot be enhanced above 50% although both cell types have the same basal rate of secretion (approximately 10% of the synthesized cathepsin D). We suggest that pH-independent sorting mechanisms contribute to the targeting of cathepsin D in U937 cells. Processing of the cathepsin D remaining in cells is characteristically changed depending on the drug. The proteolytic processing is strongly inhibited by chloroquine and is rather insensitive to monensin. Unlike the other drugs, monensin blocks the formation of complex oligosaccharides in cathepsin D and allows for extensive secretion solely of molecules that are sensitive to endo H.


Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea.
Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri The concentration of MPh suggests the cell membrane of M. acetivorans, but not of M. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh.IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans, but not Methanosarcina barkeri, has electrically quantized membranes. Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale.


Chiral versus racemic building blocks in supramolecular chemistry: malate salts of organic diamines.
(S)-Malic acid forms a salt with N,N'-dimethylpiperazine, [MeN(CH(2)CH(2))(2)NMe]H(2)(2+) x 2C(4)H(5)O(5)(-) (1) (triclinic, P1, Z' = 1), in which the cations link pairs of hydrogen-bonded anion chains to form a molecular ladder. With 4,4'-bipyridyl, (S)-malic acid forms a 1:1 adduct which crystallizes from methanol to yield two polymorphs, (2) (triclinic, P1, Z' = 1) and (3) (monoclinic, C2, Z' = 1), while racemic malic acid with 4,4'-bipyridyl also forms a 1:1 adduct, (4) (monoclinic, P2(1)/c, Z' = 1). In each of (2), (3) and (4) the components are linked by O[bond]H...N and N[bond]H...O into chains of alternating bipyridyl and malate units, which are linked into sheets by O[bond]H...O hydrogen bonds. In each of the 1:1 adducts (5) and (6), formed by, respectively, (S)-malic acid and racemic malic acid with 1,2-bis(4'-pyridyl)ethene, the diamine is disordered over two sets of sites, related by a 180 degrees rotation about the N...N vector. In (5), (C(12)H(10)N(2))H(+) x C(4)H(5)O(5)(-) (triclinic, P1, Z' = 1), the components are again linked by a combination of N[bond]H...O and O[bond]H...O hydrogen bonds into sheets, while in (6) (triclinic, P1;, Z' = 0.5) there is only partial transfer of the H atom from O to N and the malate component is disordered across a centre of inversion. With 1,4-diazabicyclo[2.2.2]octane, racemic malic acid forms a 1:2 salt, [(C(6)H(12)N(2))H(2)](2+).2C(4)H(5)O(5)(-) (7) (monoclinic, P2(1)/c, Z' = 2), while (S)-malic acid forms a 1:1 adduct, (8) (monoclinic, P2(1), Z' = 3). There are thus six independent molecular components in each. In (7) the ions are linked by an extensive series of N[bond]H...O and O[bond]H...O hydrogen bonds into a three-dimensional framework, but in (8) there is extensive disorder involving all six components, and no refinement proved to be feasible.


Effect of fentanyl on awakening concentration of sevoflurane.
This study was designed to determine if fentanyl altered MAC-awake (the end-tidal concentration of sevoflurane associated with eye opening to verbal command) in 30 healthy, ASA I patients. During anaesthesia, no other anaesthetics or drugs were given with the exception of sevoflurane. After surgery, end-tidal anaesthetic concentration was maintained constant for at least 15 min. If patients failed to respond to command, the end-tidal concentration was decreased and again maintained constant for 15 min. The anaesthetic concentration midway between the value permitting the response and that just preventing the response was recorded as MAC-awake. Fentanyl was administered at predicted plasma concentrations of 1 and 2 ng mg-1 using a computer-controlled continuous infusion and plasma concentrations of fentanyl were measured at the time of MAC-awake measurements. MAC-awake of the control group in which fentanyl was not administered was mean 0.67 (SD 0.12)% or 0.36 (0.03) MAC, being significantly higher than that of the fentanyl 2-ng ml-1 group (0.57 (0.09)% or 0.30 (0.04) MAC). In the fentanyl 1-ng ml-1 group, MAC-awake (0.65 (0.10)% or 0.34 (0.05) MAC) did not differ from that in the control group. Logistic regression analysis showed that increasing plasma concentration of fentanyl and increasing age significantly reduced the MAC-awake of sevoflurane. Because the reduction was very small relative to the overall scatter of the MAC-awake, a low plasma concentration of fentanyl did not significantly reduce the MAC-awake of sevoflurane.


Affinofile Assay for Identifying Macrophage-Tropic HIV-1.
The ability to enter monocyte-derived macrophage (MDM) in vitro is commonly used to define macrophage-tropic HIV-1 despite the fact that viruses vary continuously in their ability to enter MDMs in vitro, and MDMs vary in their ability to support HIV-1 entry (Joseph et al., 2014; Peters et al., 2006). This makes it difficult to distinguish viruses that are adapted to replicating in macrophage from those that are adapted to replicating in T cells. We use the Affinofile cell line (Johnston et al., 2009) to assay for macrophage tropism by capitalizing on the fact that macrophage-tropic HIV-1 has an enhanced ability to enter cells expressing low levels of CD4 (Joseph et al., 2014; Peters et al., 2006; Duenas-Decamp et al., 2009; Dunfee et al., 2006; Gorry et al., 2002; Martin-Garcia et al., 2006; Peters et al., 2004) and Affinofile cells can be induced to express a wide range of CD4 densities (Johnston et al., 2009). We induce Affinofile cells to express either high or low CD4, infect those cells with pseudotyped reporter virus, and quantify percent infectivity at low CD4 relative to infectivity at high CD4. Macrophage-tropic viruses have an enhanced ability to infect at low CD4. Using this approach we have found that macrophage-tropic strains of HIV-1 are relatively rare and that most HIV-1 variants require high levels of CD4 to enter cells, a phenotype we have referred to as R5 T cell-tropic.


Gadolinium retention in the body: what we know and what we can do.
Gadolinium-based contrast agents (GBCA), widely used in Magnetic Resonance Imaging (MRI) for almost 30 years, were recently shown to be deposited in the brain and to induce persistent T1 shortening in deep gray matter structures in subjects with normal renal function. The aim of the present study is to summarize the evidence derived from the rapidly growing scientific literature on Gadolinium retention in the brain and in the rest of the body. To this end, the original articles that described imaging and pathology findings in humans and animals exposed to GBCA were reviewed. The main aspects that emerged were the different effects of linear and macrocyclic GBCA on brain MRI appearance, the evidence of Gadolinium tissue retention in multiple organs, and the debated issue of the possible clinical consequences. Although no adverse health effects have been documented so far, updated information about GBCA build-up in the body is necessary for health professionals, also in view of the increasing concern in the general population. To date, our knowledge about the mechanisms of Gadolinium tissue deposition and, above all, its long-term consequences is still largely incomplete. However, while official guidelines are eagerly awaited, some advices may already be given, to help our radiological daily practice.


Syndrome of intrahepatic biliary dysgenesis and cardiovascular malformations.
Peripheral pulmonary stenosis with or without intracardiac disease is described in 14 patients with intrahepatic biliary dysgenesis. Cardiovascular malformations were not present among a large group of patients with extrahepatic biliary dysgenesis. This association of intrahepatic biliary dysgenesis and vascular malformations is postulated to be a specific malformation syndrome resulting most probably from intrauterine infection. The cardiovascular disease is usually mild. The liver dysfunction varies in severity, and is accompanied by a notable hyperlipoproteinemia with secondary xanthomata which can be ameliorated by long-term treatment with cholestyramine resin and/or vegetable oil supplements.


Reflective learning.
Good care matters. If I learned one thing from my nursing elective in Malawi, East Africa, it was this: whatever the environment or situation, good care should be at the heart of our practice.


Catalytic carbonyl addition through transfer hydrogenation: a departure from preformed organometallic reagents.
Classical protocols for carbonyl allylation, propargylation and vinylation typically rely upon the use of preformed allyl metal, allenyl metal and vinyl metal reagents, respectively, mandating stoichiometric generation of metallic byproducts. Through transfer hydrogenative C-C coupling, however, carbonyl addition may be achieved from the aldehyde or alcohol oxidation level in the absence of stoichiometric organometallic reagents or metallic reductants. Here, we review transfer hydrogenative methods for carbonyl addition, which encompass the first catalytic protocols enabling direct C-H functionalization of alcohols.


Skin-puncture and blood-collecting technique for infants: update and problems.
This is updated information on acceptable practice in skin puncture and blood collection in infants, as well as on the devices used, with the additional aim of emphasizing major problem areas and some tentative solutions. Consensus standards for skin puncture have little experimental support, and evade the hard fact that studies are needed to clarify optimum sites for puncture and depth and width of lancets, and to assess the effects of compression and skin resistance in the puncturing process. Preliminary data revealed that the puncturing depth of 2.4 mm recommended for the newborn is excessive. In four of 14 newborns at necropsy, the distance from posterior planar skin surface to underlying bone ranged between 2.0 and 2.2 mm. An experimental lancet, with a 1.8-mm tip length and a diameter of 0.79 mm yielded customary blood volumes from newborns in three of the four pediatric centers where it was tested. Lack of success with the lancet was attributed to inexperienced phlebotomists, not to the lancet's decreased size. Also reviewed are problems with common devices used, and the need for examining the "economy" of blood collection.


Advances in treatment for postpartum major depressive disorder.
Introduction: Postpartum depressive disorder (PPD) is a burdensome medical condition. To date, only one treatment (Brexanolone) has undergone registrational trials and is approved in the United States with an indication for the treatment of PPD. However, other treatments are prescribed and have been tested for this condition. Herein, the authors review the available scientific evidence pertaining to the somatic treatments of PPD. Areas covered: The authors evaluate the published open-label and randomized controlled trials (RCTs), examine the biological mechanisms of PPD treatments, and evaluate how the available data translates into information that may be useful for clinical practice. Expert opinion: Antidepressants have long been the mainstay of PPD treatment, despite the limited evidence from randomized clinical trials that supports this practice. Brexanolone improves treatment options for women with PPD. However, the relatively burdensome administration and monitoring protocol, along with the high cost of the medication, limit the possibility for an extensive use of this medication. Large, randomized, controlled trials of hormonal treatments in patients with PPD are warranted. Also, treatment with mood stabilizers and/or antipsychotics in women with major depressive disorder, who meet the DSM-5 mixed features specifiers in the post-partum period, should be tested in controlled clinical trials.


Application of High-Density Electropulsing to Improve the Performance of Metallic Materials: Mechanisms, Microstructure and Properties.
The technology of high-density electropulsing has been applied to increase the performance of metallic materials since the 1990s and has shown significant advantages over traditional heat treatment in many aspects. However, the microstructure changes in electropulsing treatment (EPT) metals and alloys have not been fully explored, and the effects vary significantly on different material. When high-density electrical pulses are applied to metals and alloys, the input of electric energy and thermal energy generally leads to structural rearrangements, such as dynamic recrystallization, dislocation movements and grain refinement. The enhanced mechanical properties of the metals and alloys after high-density electropulsing treatment are reflected by the significant improvement of elongation. As a result, this technology holds great promise in improving the deformation limit and repairing cracks and defects in the plastic processing of metals. This review summarizes the effect of high-density electropulsing treatment on microstructural properties and, thus, the enhancement in mechanical strength, hardness and corrosion performance of metallic materials. It is noteworthy that the change of some properties can be related to the structure state before EPT (quenched, annealed, deformed or others). The mechanisms for the microstructural evolution, grain refinement and formation of oriented microstructures of different metals and alloys are presented. Future research trends of high-density electrical pulse technology for specific metals and alloys are highlighted.


Effect of hypothermia and endotoxin on phagocytosis.
Experiments with colloidal 198Au indicated that gold clearance highly decreased in rabbits cooled to 29-30 degrees C. The capacity of storing colloidal gold decreased especially in the spleen and liver. Endotoxin reduced the gold clearance in normothermic rabbits; the decrease was more marked in hypothermic animals.


Gain Control in Predictive Smooth Pursuit Eye Movements: Evidence for an Acceleration-Based Predictive Mechanism.
The smooth pursuit eye movement system incorporates various control features enabling adaptation to specific tracking situations. In this work, we analyzed the interplay between two of these mechanisms: gain control and predictive pursuit. We tested human responses to high-frequency perturbations during step-ramp pursuit, as well as the pursuit of a periodically moving target. For the latter task, we found a nonlinear interaction between perturbation response and carrier acceleration. Responses to perturbations where the initial perturbation acceleration was contradirectional to carrier acceleration increased with carrier velocity, in a manner similar to that observed during step-ramp pursuit. In contrast, responses to perturbations with ipsidirectional initial perturbation and carrier acceleration were large for all carrier velocities. Modeling the pursuit system suggests that gain control and short-term prediction are separable elements. The observed effect may be explained by combining the standard gain control mechanism with a derivative-based short-term predictive mechanism. The nonlinear interaction between perturbation and carrier acceleration can be reproduced by assuming a signal saturation, which is acting on the derivative of the target velocity signal. Our results therefore argue for the existence of an internal estimate of target acceleration as a basis for a simple yet efficient short-term predictive mechanism.


Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity.
The flavonoid luteolin has various pharmacological activities. However, few studies exist on the in vivo mechanism underlying the actions of luteolin in hepatic steatosis and obesity. The aim of the current study was to elucidate the action of luteolin on obesity and its comorbidity by analyzing its transcriptional and metabolic responses, in particular the luteolin-mediated cross-talk between liver and adipose tissue in diet-induced obese mice. C57BL/6J mice were fed a normal, high-fat, and high-fat + 0.005% (weight for weight) luteolin diet for 16 weeks. In high fat-fed mice, luteolin improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption. In adipose tissue, luteolin increased PPARγ protein expression to attenuate hepatic lipotoxicity, which may be linked to the improvement in circulating fatty acid (FA) levels by enhancing FA uptake genes and lipogenic genes and proteins in adipose tissue. Interestingly, luteolin also upregulated the expression of genes controlling lipolysis and the tricarboxylic acid (TCA) cycle prior to lipid droplet formation, thereby reducing adiposity. Moreover, luteolin improved hepatic insulin sensitivity by suppressing SREBP1 expression that modulates Irs2 expression through its negative feedback and gluconeogenesis. Luteolin ameliorates the deleterious effects of diet-induced obesity and its comorbidity via the interplay between liver and adipose tissue.


Genetic Background of β-Thalassemia in Northeast Algeria with Assessment of the Thalassemia Severity Score and Description of a new β0-Thalassemia Frameshift Mutation (HBB: c.374dup; p.Pro126Thrfs*15).
β-Thalassemia (β-thal) is a genetic disorder representing a major health problem in Algeria. Our first objective was to determine the allelic frequencies and molecular spectrum of β-thal mutations in patients with major hemoglobinopathies [β-thal major (β-TM) and sickle cell disease] in three provinces of northeast Algeria. Our second objective was to assess if the clinical management of β-TM patients depended on their region of origin. Our last objective was to assess a population originating from Maghreb, the reliability of the thalassemia severity score (TSS) for patients with homozygous β-thal. Sanger HBB gene sequencing was performed on 59 patients with sickle cell disease and 60 with β-TM. For the latter patients, the genetic modifiers of the TSS were genotyped: α-thalassemia (α-thal) deletions and four Hb F-inducing polymorphisms (XmnI, rs1427407 and rs10189857 for BCL11A and rs9399137 for HMIP). Eleven different β-thal mutations were found but two of them (HBB: c.118C>T and HBB: c.93-21G>A) accounted for about 70.0% of the β-thal alleles. A relatively high proportion of Hb S (HBB: c.20A>T)/β-thal genotypes (27.0%) was found in our sickle cell disease cohort where a new frameshift β0-thal mutation (HBB: c.374dup; p.Pro126Thrfs*15) was identified. No difference was found in the three provinces. Of the 60 β-TM patients, those with a high or very high TSS were significantly younger at the age of first transfusion, thus assessing the reliability of this scoring system in a Maghrebin cohort. Trends for a lower age of splenectomy and high ferritin levels were also detected for the higher TSS categories.


Anticancer Drug-Induced Epithelial-Mesenchymal Transition via p53/miR-34a axis in A549/ABCA3 Cells.
Several anticancer drugs including bleomycin (BLM) and methotrexate (MTX) cause serious lung diseases such as pulmonary fibrosis. Although evidences showing the association of epithelial-mesenchymal transition (EMT) with pulmonary fibrosis are increasing, the mechanism underlying anticancer drug-induced EMT has been poorly understood. On the other hand, miR-34a, a non-coding small RNA, has been highlighted as a key factor to regulate EMT in lung. In this study, we elucidated the role of miR-34a in anticancer drug-induced EMT using A549/ABCA3 cells as a novel type II alveolar epithelium model. Expression levels of α-smooth muscle actin (α-SMA) mRNA, miR-34a, and p53 were evaluated by real-time PCR and western blot analysis, respectively. BLM and MTX induced EMT-like morphological changes and increase in mRNA expression level of α-SMA, an EMT marker. Also, both drugs increased the expression level of miR-34a. Furthermore, mRNA expression level of α-SMA was enhanced by introduction of miR-34a mimic into A549/ABCA3 cells. To examine the mechanism underlying drug-induced enhancement of miR-34a expression, we focused on p53/miR-34a axis. Both drugs upregulated protein expression of p53, an inducer of miR-34a, as well as phosphorylation of Ser15 in p53. These findings indicated that p53/miR-34a axis may contribute to anticancer drug-induced EMT in type II alveolar epithelial cells.


Emerging methods in comparative effectiveness and safety: symposium overview and summary.
Interest in new methods for comparative effectiveness, drug and patient safety, and related studies is burgeoning. The advent of Medicare Part D for outpatient prescription drugs has drawn significant attention to the need for efficient ways to monitor the potential benefits and harms of pharmaceuticals. These trends prompted the Effective Health Care program at the Agency for Healthcare Research and Quality and its DEcIDE (Developing Evidence to Inform Decisions about Effectiveness) network to examine innovative approaches for such investigations through an invitational symposium in June 2006. Conference papers covered numerous points about ways to structure both interventional and database-oriented studies, particularly those concerned with adverse drug events, to avoid bias in those studies, and to apply advanced statistical tools to exploit the information from these studies to their fullest. Of particular importance are: (1) using new types of experimental designs, including cluster randomization, delayed designs, pragmatic trials, and practice-based investigations that incorporate the natural variation of data from routine clinical practice; (2) finding efficient ways to use different types of databases-eg, Department of Veterans Affairs files, Centers for Disease Control and Prevention surveillance files, Medicaid claims data, and state hospital data-for examining initiation, persistence, and adherence, and the benefits and adverse events of pharmaceutical use; and (3) inventing or refining ways to decrease the threats to validity of analyses relying on administrative or other observational data, particularly through propensity scoring, inverse probability weighting, risk adjustment, and direct or indirect methods for synthesizing comparative effectiveness information.


[Continuous lateral rotation or kinetic therapy: an update of knowledge].
Acute lung injury and, when extreme, acute respiratory distress syndrome, are thought to be expression of a diffuse and overwhelming inflammatory reaction of the pulmonary capillary membrane to a variety of causes. The ventilatory support is essential in this patients. In the last years we know the significance of the postural treatment in this type of patients through the prone positioning. The continuous lateral rotation therapy or kinetic therapy (KT) is the new manner by other positioning beside the technological advances. Lowly it's introducing in our setting. The follow article would respound the next questions: What's the KT? How must to make the KT? What recommendations have been offered by specialists from the complications? Which is it efectivity?


Does calcium deposition play a role in the stability of atheroma? Location may be the key.
Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The role of calcium deposition and its contribution to plaque stability is controversial. This study uses both an idealized and a patient-specific model to evaluate the effect of a calcium deposit on the stress distribution within an atheromatous plaque. Using a finite-element method, structural analysis was performed on an idealized plaque model and the location of a calcium deposit within it was varied. In addition to the idealized model, in vivo high-resolution MR imaging was performed on 3 patients with carotid atheroma and stress distributions were generated. The individual plaques were chosen as they had calcium at varying locations with respect to the lumen and the fibrous cap. The predicted maximum stress was increased by 47.5% when the calcium deposit was located in the thin fibrous cap in the model when compared with that in a model without a deposit. The result of adding a calcium deposit either to the lipid core or remote from the lumen resulted in almost no increase in maximal stress. Calcification at the thin fibrous cap may result in high stress concentrations, ultimately increasing the risk of plaque rupture. Assessing the location of calcification may, in the future, aid in the risk stratification of patients with carotid stenosis.


Finding query suggestions for PubMed.
It is common for PubMed users to repeatedly modify their queries (search terms) before retrieving documents relevant to their information needs. To assist users in reformulating their queries, we report the implementation and usage analysis of a new component in PubMed called Related Queries, which automatically produces query suggestions in response to the original user's input. The proposed method is based on query log analysis and focuses on finding popular queries that contain the initial user search term with a goal of helping users describe their information needs in a more precise manner. This work has been integrated into PubMed since January 2009. Automatic assessment using clickthrough data show that each day, the new feature is used consistently between 6% and 10% of the time when it is shown, suggesting that it has quickly become a popular new feature in PubMed.


Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals.
Cytokines produced by T helper (Th) cells are important in orchestrating the immune response during health and disease. Recent reports indicated that cytokine mRNA expression in foals is often quantitatively lower than that of adult horses suggesting that foal T cells are not fully mature. Here, peripheral blood mononuclear cells from foals and adult horses were stimulated with phorbol 12-myristate 13-acetate and analyzed for intracellular interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-10 production, representing the Th1, Th2 and regulatory TR1 cell phenotypes respectively, by flow cytometry. In agreement with previous reports, all three cytokines were quantitatively reduced in foals compared to adults. However, the balance between Th1 and Th2 cytokines (IFN-gamma/IL-4 ratio) showed a clear Th1-biased response in foals by 6 and 12 weeks of life, while similar IFN-gamma/IL-10 ratios were found in foals and adult horses. By day 5 after birth, intracellular IFN-gamma production by foal CD4+ and CD8+ T cells resembled that in adults. Overall, IL-4 production was low in foals. IL-4+ cells peaked at day 5 of age when IL-4 was mainly produced by IgE+ cells. Relative percentages of IL-4+ Th2 cells were significantly lower in foals at all time points. The data suggested that equine neonates and young foals have an impaired Th2 response, that the immune response of foals is Th1 biased, that IFN-gamma production by Th and cytotoxic T cells is qualitatively similar to adult horses, and regulatory IL-10 production by T cells is developmentally mature in foals during the first three months of life.


Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study.
Renal failure, both acute and chronic, is a common complication after liver transplantation and can seriously jeopardise long-term outcome. Given organ shortage it should be essential to determine which patients will experience progressive and severe renal dysfunction after liver transplantation (LT). To correlate pre-transplant renal function and risk factors for renal failure after liver transplantation with occurrence of renal failure at 1 and 5 years after LT, with particular attention to hepatitis C virus (HCV) infection. Data from patients enrolled in the liver section of Neoral MOST (Multinational Observational Study in Transplantation) study were used for the analysis. HCV status, pre-transplant serum creatinine level, recipient gender, recipient age, pre-transplant arterial hypertension, pre-transplant diabetes mellitus, pre-transplant antiviral therapy, the time of the transplant (before or after 2000) and immunosuppressive regimen were collected for each patient. Post-transplant occurrence of renal failure at 1 and 5 years was defined as a GFR<60 mL/min/1.73 m(2) (Stage III of the National Kidney Foundation). Data from 1948 patients enrolled in the study were considered. Glomerular filtration rate (GFR) was evaluated in 406 patients at 1 year and in 233 patients at 5 years after LT. The prevalence of HCV infection was 35% in the former and 37% in the latter. The median GFR was 70 mL/min/1.73 m(2) after 1 year and 69 mL/min after 5 years, significantly lower in HCV-positive (HCV+) than in HCV-negative (HCV-) patients both 1 and 5 years after LT (p<0.001). GFR before transplant correlated with GFR at 1 month, 1 and 3 years (p<0.0001 for all correlations). Multivariate analysis confirmed HCV status, pre-LT serum creatinine levels and recipient gender as significant predictors of 1-year GFR (p<0.001 for all three). Further analysis of the effect of recipient gender indicated that the only significant risk factor observed in both male and female patients was HCV positivity. Only 1-year GFR was an independent predictor of 5-year GFR (p<0.001). HCV+ status, cyclosporine (CsA) exposure, antiviral therapy and diabetes mellitus had no significant influence on 5-year GFR. HCV status and pre-LT serum creatinine levels were independent predictors of renal function a year after LT, together with GFR before transplant. The negative impact of HCV positivity on renal function was not confirmed in the long term, whereas the prognostic influence of an abnormal renal function in the early post-transplant period was more persistent.


[Physical mapping of the immunity region of phage phi 80].
Mapping of the sites of cleavage of five restriction endonucleases (BglI, BglII, EcoRV, KpnI and PvuII) in the immunity region of bacteriophage phi 80 DNA is described. The order of the 27 restriction sites was established. This helped to localize the phi 80 cI gene within the 640 bp fragment of the immunity region. Recombinant plasmids carrying phi 80 "kil" function were constructed. The function is suppressed by the cI-coded repressor. The deletion AB43 which is present in the phi 80 vir mutant is located within the phi 80 DNA fragment carrying the cI gene.


Test procedure for artificial mitral valves.
The flow curve of a valve-tester has a great influence on the performance of a valve. Usually the flow curve of the aorta is used. However, the mitral valve flow curve differs greatly from the flow curve of the aortic valve. It varies with the pulse rate and is further changed in patients with certain heart diseases. To investigate the different mitral flow conditions, ultrasonic flow curves from patients with a mechanical artificial mitral valve were analyzed. The curves show that a mitral valve prosthesis has not only to work under physiological flow conditions, but also in pathologically deviant flows. According to these results three different characteristic flow curves were selected and used to test several valves with a computer controlled valve-tester. The mean diastolic pressure difference and the whole closing behavior were influenced by the flow curve; and the differences in energy losses were particularly great. This indicates, that the flow curve must be adjusted appropriately.


[Understanding the sexuality of HVI-1 carriers].
The objective of the present investigation was to identify the sexual difficulties experienced by persons in an HIV-1 crisis. This is a study of a descriptive nature based on the Theory of Crisis. The sample consisted of 5 patients with HIV-1 followed up clinically in a town in the hinterland of the state of São Paulo. Semistructured interviews were tape recorded and transcribed. Data were analyzed according to MEIHY (1996) and BARDIN (1994). We conclude that the subjects presented a negative adaptation with respect to sexual, social and emotional difficulties. The results indicate the need for effective nursing interventions with persons in an HIV-1 crisis.


Compensators for dose and scatter management in cone-beam computed tomography.
The ability of compensators (e.g., bow-tie filters) designed for kV cone-beam computed tomography (CT) to reduce both scatter reaching the detector and dose to the patient is investigated. Scattered x rays reaching the detector are widely recognized as one of the most significant challenges to cone-beam CT imaging performance. With cone-beam CT gaining popularity as a method of guiding treatments in radiation therapy, any methods that have the potential to reduce the dose to patients and/or improve image quality should be investigated. Simple compensators with a design that could realistically be implemented on a cone-beam CT imaging system have been constructed to determine the magnitude of reduction of scatter and/or dose for various cone-beam CT imaging conditions. Depending on the situation, the compensators were shown to reduce x-ray scatter at the detector and dose to the patient by more than a factor of 2. Further optimization of the compensators is a possibility to achieve greater reductions in both scatter and dose.


[A pilot study of selective screening for high risk children with inborn error of metabolism using tandem mass spectrometry in China].
The new technology of tandem mass spectrometry is exerting a significant impact on the diagnostics of inborn metabolic errors, and allows to detect a number of these disorders in a single step. The aim of the present study was to establish a dry blood filter paper method for amino acid and acylcarnitine profiles test using tandem mass spectrometry and to apply the method for selective screening in high risk children with inborn error of metabolism. The study group consisted of 104 high risk cases of inborn error of metabolism from 5 pediatric hospitals in Shanghai and Beijing were tested from November 2002 to June 2003; 77 were males and 27 females, the means age was 4.8 +/- 4.2 years. These patients had mental retardation, slow development, psychological abnormalities, muscle hypotonia, jaundice, hepatosplenomegaly, recurrent vomiting, and convulsion. Laboratory examinations suggested metabolic acidosis, hypoglycemia, hyperammonemia and hyperlactacidemia. Phenylketonuria was excluded in this study by routine phenylalanine screening. The control group consisted of 308 children, 170 males and 138 females. The blood was collected on filter paper, punched and extracted into methanol solution with stable isotope labeled internal standards, then derivatized with butanolic-HCl. After preparation, the samples were analyzed by tandem mass spectrometry (API 2000). Ten of 104 patients (9.6%) were positive in our selective screening program, including one with tyrosinemia, one with homocystinuria, one with hyperornithinemia, two with methylmalonic acidemia, one with propionic acidemia, one with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, two with medium chain acyl-CoA dehydrogenase deficiency, and one with carnitine palmitoyl transferase type II deficiency. The authors established a fast, accurate and sensitive tandem mass spectrometry method for amino acid and acylcarnitine profiles analysis, nearly 30 metabolic diseases including amino acid disorders, organic acid disorders and fatty acid oxidation disorders could be detected, most of the diseases that cause death and disability represent preventable entities by early diagnosis and treatment. The results indicated the importance of selective screening for high risk patients with inborn error of metabolism.


Characterization of Micropolyspora faeni antigens.
Culture filtrate antigens of Micropolyspora faeni grown in a synthetic medium in a stirred fermentor were characterized. The culture filtrate antigens were fractionated by preparative isoelectric focusing with a pH gradient of 3.5 to 5.5. The fractions were pooled according to their reaction with rabbit anti-M. faeni sera. A pool containing two major antigens which were resolved by analytical isoelectric focusing and polyacrylamide disc gel electrophoresis was obtained. One antigen was stainable with Coomassie blue and periodic acid-Schiff stain and was determined to have a mass of 51,000 daltons. The other antigen was stainable only with Coomassie blue and was determined to have a mass of 29,000 daltons. When used at 1 mg/ml, this pool reacted with the sera from all patients with farmer's lung disease by immunodiffusion but failed to react with control sera.


Gaussian Graphical Models Reveal Inter-Modal and Inter-Regional Conditional Dependencies of Brain Alterations in Alzheimer's Disease.
Alzheimer's disease (AD) is characterized by a sequence of pathological changes, which are commonly assessed in vivo using various brain imaging modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET). Currently, the most approaches to analyze statistical associations between regions and imaging modalities rely on Pearson correlation or linear regression models. However, these models are prone to spurious correlations arising from uninformative shared variance and multicollinearity. Notably, there are no appropriate multivariate statistical models available that can easily integrate dozens of multicollinear variables derived from such data, being able to utilize the additional information provided from the combination of data sources. Gaussian graphical models (GGMs) can estimate the conditional dependency from given data, which is conceptually expected to closely reflect the underlying causal relationships between various variables. Hence, we applied GGMs to assess multimodal regional brain alterations in AD. We obtained data from N = 972 subjects from the Alzheimer's Disease Neuroimaging Initiative. The mean amyloid load (AV45-PET), glucose metabolism (FDG-PET), and gray matter volume (MRI) were calculated for each of the 108 cortical and subcortical brain regions. GGMs were estimated using a Bayesian framework for the combined multimodal data and the resulted conditional dependency networks were compared to classical covariance networks based on Pearson correlation. Additionally, graph-theoretical network statistics were calculated to determine network alterations associated with disease status. The resulting conditional dependency matrices were much sparser (≈10% density) than Pearson correlation matrices (≈50% density). Within imaging modalities, conditional dependency networks yielded clusters connecting anatomically adjacent regions. For the associations between different modalities, only few region-specific connections were detected. Network measures such as small-world coefficient were significantly altered across diagnostic groups, with a biphasic u-shape trajectory, i.e., increased small-world coefficient in early mild cognitive impairment (MCI), similar values in late MCI, and decreased values in AD dementia patients compared to cognitively normal controls. In conclusion, GGMs removed commonly shared variance among multimodal measures of regional brain alterations in MCI and AD, and yielded sparser matrices compared to correlation networks based on the Pearson coefficient. Therefore, GGMs may be used as alternative to thresholding-approaches typically applied to correlation networks to obtain the most informative relations between variables.


Peroxidase activity in rat liver microbodies after amino-triazole inhibition.
The in vivo effects of 3-amino-1,2,4-triazole (AT) on the fine structure of microbodies in hepatic cells of male rats has been studied by the peroxidase-staining technique. Within 1 hr of intraperitoneal injection AT abolishes microbody peroxidase-staining, and the return of staining coincides temporally with the known pattern of return of catalase activity following AT inhibition; this is further evidence that the peroxidase staining of microbodies is due to catalase activity. Peroxidase staining reappears in the microbody matrix without evidence of either massive degradation or rapid proliferation of the organelles. Furthermore, during the period of return of activity, ribosomal staining occurs adjacent to microbodies whose matrix shows little or no peroxidase staining. These observations are interpreted as evidence that (a) catalase is capable of entering preexisting microbodies without traversing the cisternae of the rough endoplasmic reticulum or the Golgi apparatus, and that (b) the ribosomal staining is probably not cytochemical diffusion artifact and may represent a localized site of synthesis or activation of catalase.


Dependence of the Substituent Effect on Solvent Properties.
The influence of a solvent on the substituent effect (SE) in 1,4-disubstituted derivatives of benzene (BEN), cyclohexa-1,3-diene (CHD), and bicyclo[2.2.2]octane (BCO) is studied by the use of polarizable continuum model method. In all X-R-Y systems for the functional group Y (NO2, COOH, OH, and NH2), the following substituents X have been chosen: NO2, CHO, H, OH, and NH2. The substituent effect is characterized by the charge of the substituent active region (cSAR(X)), substituent effect stabilization energy (SESE), and substituent constants σ or F descriptors, the functional groups by cSAR(Y), whereas π-electron delocalization of transmitting moieties (BEN and CHD) is characterized by a geometry-based index, harmonic oscillator model of aromaticity. All computations were carried out by means of B3LYP/6-311++G(d,p) method. An application of quantum chemistry SE models (cSAR and SESE) allows to compare the SE in water solutions and in the gas phase. Results of performed analyses indicate an enhancement of the SE by water. The obtained Hammett-type relationships document different nature of interactions between Y and X in aromatic and olefinic systems (a coexistence of resonance and inductive effects) than in saturated ones (only the inductive effect). An increase of electric permittivity clearly enhances communications between X and Y for BEN and CHD systems.


Inhibition of PKCepsilon improves glucose-stimulated insulin secretion and reduces insulin clearance.
In type 2 diabetes, pancreatic beta cells fail to secrete sufficient insulin to overcome peripheral insulin resistance. Intracellular lipid accumulation contributes to beta cell failure through poorly defined mechanisms. Here we report a role for the lipid-regulated protein kinase C isoform PKCepsilon in beta cell dysfunction. Deletion of PKCepsilon augmented insulin secretion and prevented glucose intolerance in fat-fed mice. Importantly, a PKCepsilon-inhibitory peptide improved insulin availability and glucose tolerance in db/db mice with preexisting diabetes. Functional ablation of PKCepsilon selectively enhanced insulin release ex vivo from diabetic or lipid-pretreated islets and optimized the glucose-regulated lipid partitioning that amplifies the secretory response. Independently, PKCepsilon deletion also augmented insulin availability by reducing both whole-body insulin clearance and insulin uptake by hepatocytes. Our findings implicate PKCepsilon in the etiology of beta cell dysfunction and highlight that enhancement of insulin availability, through separate effects on liver and beta cells, provides a rationale for inhibiting PKCepsilon to treat type 2 diabetes.


Treatment of toilet wastewater for reuse in a membrane bioreactor.
Toilet wastewater is treated and reused on site at Europe's highest membrane bioreactor (MBR), located in a cable car mountain station in the ski resort of Zermatt. Negative impacts on the sensitive mountain environment are minimised by reusing close to 100% of the treated wastewater for toilet flushing. Besides 100% nitrogen removal, 80% of phosphorus was also eliminated. This paper presents operational results, optimisations of sludge management, decoloration and long-term maintenance of biomass in the very low-loaded summer season. From a global view the experiences and results of the project are of great importance, proposing a solution to a problem existing 100-fold in the Alps as well as in arid regions all over the world: reducing water consumption for sanitation by reuse.


Soliton Pulse Propagation in the Presence of Disorder-Induced Multiple Scattering in Photonic Crystal Waveguides.
We introduce a new coupled mode theory to model nonlinear Schrödinger equations for counterpropagating Bloch modes that include disorder-induced multiple scattering effects on nonlinear soliton propagation in photonic crystal waveguides. We also derive subunit-cell coupling coefficients and use these to introduce a generalized length scale associated with each coupling effect. In particular, we define a multiple-scattering length scale that quantifies the spatial extent of a disorder-induced cavity mode. Our numerical simulations of nonlinear pulse propagation are in excellent qualitative agreement with recent experiments and provide insight into how structural disorder inhibits soliton propagation and other nonlinear propagation effects in photonic crystal waveguides.


Leptospirosis in a midland rural area of Kerala State.
Leptospirosis has been repeatedly reported from the State of Kerala since 1989 and is one of the commonest diseases among the 14 notifiable diseases in the district level communicable disease surveillance system. As there are no field studies on human leptospirosis in Kerala, we undertook this seroepidemiological study of leptospirosis in the two hamlets of Ernakulam district in Kerala to identify locally prevalent serogroups, and to understand local epidemiological features of the disease. Blood samples were collected for five consecutive years from persons willing to subject themselves for the study from the selected areas (Kunnackal and Kunnakkurudy hamlets). Animal studies were conducted among samples from rodents captured from the area by the human volunteers themselves. Antibody titres were determined by microscopic agglutination test (MAT). The investigators inspected all the houses and surrounding land of the study subjects in this period. Of the 385 persons enrolled, 29.6 per cent showed evidence of past leptospiral infection. Many locally prevalent serogroups and changing patterns of prevalence in humans were identified in the five consecutive years of the study. The major serogroups were autumnalis, louisiana, australis, and grippotyphosa. Rodents showed 11 per cent seropositivity. Bandicoota indica showed the highest seropositivity (44.4%). Our findings showed that the physical environment of the study area was favourable for prolonged survival of leptospires. Farming practices exposed the human volunteers to soil and surface water and leptospirosis is endemically present here. Majority of seropositive individuals in the community had only subclinical infection. Rodents were abundant and contributed to enzootic and endemic prevalence of leptospirosis.


Destination memory in traumatic brain injuries.
Destination memory, which is socially driven, refers to the ability to remember to whom one has sent information. Our study investigated destination memory in patients with traumatic brain injuries (TBIs). Patients and control participants were invited to tell proverbs (e.g., "the pen is mightier than the sword") to pictures of celebrities (e.g., Barack Obama). Then they were asked to indicate to which celebrity they had previously told the proverbs. Besides the assessment of destination memory, participants performed a binding task in which they were required to associate letters with their corresponding location. Analysis demonstrated less destination memory and binding in patients with TBIs than in controls. In both populations, significant correlations were observed between destination memory and performances on the binding task. These findings demonstrate difficulty in the ability to attribute information to its appropriate destination in TBI patients, perhaps owing to difficulties in binding separate information together to form a coherent representation of an event in memory.


Investigating oxidative stress and inflammatory responses elicited by silver nanoparticles using high-throughput reporter genes in HepG2 cells: effect of size, surface coating, and intracellular uptake.
Silver nanoparticles (Ag NP) have been shown to generate reactive oxygen species; however, the association between physicochemical characteristics of nanoparticles and cellular stress responses elicited by exposure has not been elucidated. Here, we examined three key stress-responsive pathways activated by Nrf-2/ARE, NFκB, and AP1 during exposure to Ag NP of two distinct sizes (10 and 75 nm) and coatings (citrate and polyvinylpyrrolidone), as well as silver nitrate (AgNO3), and CeO2 nanoparticles. The in vitro assays assessed the cellular response in a battery of stable luciferase-reporter HepG2 cell lines. We further assessed the impact of Ag NP and AgNO3 exposure on cellular redox status by measuring glutathione depletion. Lastly, we determined intracellular Ag concentration by inductively coupled plasma mass spectroscopy (ICP-MS) and re-analyzed reporter-gene data using these values to estimate the relative potencies of the Ag NPs and AgNO3. Our results show activation of all three stress response pathways, with Nrf-2/ARE displaying the strongest response elicited by each Ag NP and AgNO3 evaluated here. The smaller (10-nm) Ag NPs were more potent than the larger (75-nm) Ag NPs in each stress-response pathway, and citrate-coated Ag NPs had higher intracellular silver concentrations compared with both PVP-coated Ag NP and AgNO3. The cellular stress response profiles after Ag NP exposure were similar to that of AgNO3, suggesting that the oxidative stress and inflammatory effects of Ag NP are likely due to the cytotoxicity of silver ions.


Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease.
The gene-regulatory landscape of the brain is highly dynamic in health and disease, coordinating a menagerie of biological processes across distinct cell types. Here, we present a multi-omic single-nucleus study of 191,890 nuclei in late-stage Alzheimer's disease (AD), accessible through our web portal, profiling chromatin accessibility and gene expression in the same biological samples and uncovering vast cellular heterogeneity. We identified cell-type-specific, disease-associated candidate cis-regulatory elements and their candidate target genes, including an oligodendrocyte-associated regulatory module containing links to APOE and CLU. We describe cis-regulatory relationships in specific cell types at a subset of AD risk loci defined by genome-wide association studies, demonstrating the utility of this multi-omic single-nucleus approach. Trajectory analysis of glial populations identified disease-relevant transcription factors, such as SREBF1, and their regulatory targets. Finally, we introduce single-nucleus consensus weighted gene coexpression analysis, a coexpression network analysis strategy robust to sparse single-cell data, and perform a systems-level analysis of the AD transcriptome.


Band gaps in the propagation and scattering of surface water waves over cylindrical steps.
Here we investigate the propagation and scattering of surface water waves in the presence of arrays of bottom-mounted cylindrical steps. Both periodic and random arrangements of the steps are considered. The wave transmission through the arrays is computed using the multiple scattering method based upon a recently derived formulation. For the periodic case, the results are compared to the band structure calculation. We demonstrate that complete band gaps can be obtained in such a system. Furthermore, we show that the randomization of the location of the steps can significantly reduce the transmission of water waves. Comparison with other systems is also discussed.


Analysis of silver binding nucleolar organizer regions in exfoliative cytology smears of potentially malignant and malignant oral lesions.
Nucleolar organizer regions are nucleolar components that contain proteins that are stained selectively by silver methods; they can be identified as black dots throughout the nucleolus and are known as silver binding nucleolar organizer regions (AgNOR). The number of AgNOR is related to the cell cycle and the proliferative activity of the cells. We investigated AgNOR using exfoliative cytology smears of potentially malignant oral lesions. Eighty individuals were divided into four equal groups: healthy controls, oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma. The mean number of AgNOR in each study group gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. The proliferative index was increased in the oral premalignant and malignant patients compared to normal subjects. The mean AgNOR size gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. Spherical shaped AgNOR were most common in controls, whereas large, clustered and kidney shapes were most common in oral squamous cell carcinoma. Multiparameter analysis of AgNOR in oral exfoliative smears is a simple, sensitive and cost-effective method for differentiating premalignant from malignant lesions and can be used in conjunction with routine cytomorphological evaluation.


Analysis of national and subnational prevalence of adolescent pregnancy and changes in the associated sexual behaviours and sociodemographic determinants across three decades in Ghana, 1988-2019.
Understanding the determinants of adolescent pregnancy and how they have changed over time is essential for measuring progress and developing strategies to improve adolescent reproductive health. This study examined changes over time in the prevalence and determinants of adolescent pregnancy in Ghana. A total of 11 nationally representative surveys from the Ghana Demographic and Health Survey (1988, 1993, 1998, 2003, 2008, 2014), Multiple Indicator Cluster Survey (2006, 2011, 2017-2018) and Malaria Indicator Survey (2016 and 2019) provided data on 14 556 adolescent girls aged 15-19 for this analysis. A random-effect meta-analysis, time trends and multivariable logistic regression models were used to track the prevalence and determinants of adolescent pregnancy. The pooled prevalence of adolescent pregnancy in Ghana was 15.4% (95% CI=13.49% to 17.30%). Rural areas (19.5%) had a higher prevalence of adolescent pregnancy than urban areas (10.6%). In the overall sample, middle adolescents (15-17 years) (aOR=0.30, 95% CI=0.23 to 0.39), adolescents in urban areas (aOR=0.56, 95% CI=0.43 to 0.74), large households (aOR=0.62, 95% CI=0.49 to 0.78), not working (aOR=0.62, 95% CI=0.43 to 0.90) and those unaware of contraceptive methods (aOR=0.49, 95% CI=0.27 to 0.90) were less likely to become pregnant. Adolescents from middle-income (aOR=0.91, 95% CI=0.67 to 1.24) or high-income (aOR=0.59, 95%CI=0.36 to 0.94) households, those who were semiliterate (aOR=0.56, 95%CI=0.39 to 0.82) or literate (aOR=0.28, 95%CI=0.21 to 0.37) and those with fewer previous sex partners were less likely to become pregnant. Not all determinants in the overall sample were consistently associated with adolescent pregnancy in the last three decades. Between 1988 and 1998, determinants of adolescent pregnancy were age, literacy, employment, household size and whether the mother was alive. Between 2003 and 2008, age, literacy, household size, income, age of last sexual partner, number of previous partners and contraception knowledge determined adolescent pregnancy. From 2011 to 2019, age, residence, literacy and menstrual cycle knowledge were determinants of adolescent pregnancy. Interventions and policies to prevent adolescent pregnancy should prioritise adolescents from disadvantaged backgrounds.


AGO2 Negatively Regulates Type I Interferon Signaling Pathway by Competition Binding IRF3 with CBP/p300.
Viral infection triggers a series of signaling cascades and host innate immune responses, including interferon (IFN) production, which depends on coordinated activity of multiple transcription factors. IFN regulatory factor 3 (IRF3) and transcriptional coactivator CREB binding protein (CBP) and/or p300 are core factors that participate in transcriptional complex formation in the nucleus. In general, cells balance the production of IFNs through suppressive and stimulative mechanisms, but viral infections can disrupt such equilibrium. This study determined that H5N1 viral infection reduced the distribution of human argonaute 2 (AGO2) in A549 cell nucleus. AGO2 did not block phosphorylation, nuclear translocation, and DNA binding ability of IRF3 but inhibited its association with CBP. Therefore, this newly revealed mechanism shows that cellular response leads to transfer of AGO2 from cell nucleus and promotes IFN-β expression to increase host survival during viral infection.


Assessing the impact of age on everyday cognitive function with a virtual environment task: The EcoKitchen.
More realistic assessment tools are imperative for a better understanding of the impact of age-related cognitive deficits on functional status. With this in mind, we probed the ability of the EcoKitchen, a non-immersive virtual environment task with increasing executively demanding kitchen chores, to detect the effects of aging on the simulated everyday functioning of healthy adults. Fifty-three adults (age between 23 and 77 years) were assessed with the EcoKitchen and a set of conventional paper-and-pencil neuropsychological tests. The associations between the baseline features of study participants and each of the two different assessment methods were examined. The associations between the EcoKitchen variables and an executive composite score were also explored. Our results showed that older individuals present deficits in the performance of both the EcoKitchen task and standard assessment methods. Notably, we found that, unlike conventional tests, accuracy in the EcoKitchen task was not related to the education level and IQ score of participants. Moreover, the EcoKitchen performance time was significantly correlated with executive tests. We have demonstrated that the EcoKitchen task, an ecologically relevant computerized neuropsychological assessment tool, might be more suitable than classic paper-and-pencil tests to capture the impact of aging on everyday cognitive function, as it proved to be less prone to the influence of confounding factors. Additionally, we have shown that executive function plays an important role in the timely performance of cognitively challenging virtual environment tasks.


Management of post-traumatic ischaemic ileal stricture using intraoperative indocyanine green fluorescence-guided resection.
Blunt abdominal trauma can affect mesenteric circulation which may lead to bowel strictures. Indocyanine green (ICG) angiography can be used to assess mesenteric blood flow and bowel perfusion as a guide to resect length intraoperatively. But this concept has not been applied to ischaemic bowel strictures. We present a case of ischaemic ileal stricture induced by blunt abdominal trauma which was managed by resection and anastomosis. Intraoperative near-infrared (NIR) ICG angiography was used as a guide to resect the bowel length. This case emphasises that ischaemic bowel strictures should be suspected in patients presenting with intestinal obstruction following trauma. Resection and anastomosis of the affected segment remains the primary treatment modality with excellent outcomes. NIR ICG angiography is a real-time objective and useful resource for assessing bowel perfusion and could be used to determine the length of the segment to be resected in patients with ischaemic bowel stricture.


Origin of end-of-aging and subaging scaling behavior in glassy dynamics.
Linear response functions of aging systems are routinely interpreted using the scaling variable t(obs)/t(w)(mu), where t(w) is the time at which the field conjugated to the response is turned on or off, and where t(obs) is the "observation" time elapsed from the field change. The response curve obtained for different values of t(w) are usually collapsed using values of mu slightly below one, a scaling behavior generally known as subaging. Recent spin glass thermoremanent magnetization experiments have shown that the value of mu is strongly affected by the form of the initial cooling protocol [G. F. Rodriguez, Phys. Rev. Lett. 91, 037203 (2003)], and even more importantly [G. G. Kenning, Phys. Rev. Lett. 97, 057201 (2006)], that the t(w) dependence of the response curves vanishes altogether in the limit t(obs)>>t(w). The latter result shows that t(obs)/t(w)(mu) scaling of linear response data cannot be generally valid, thereby casting some doubt on the theoretical significance of the exponent mu . In this work, a common mechanism is proposed for the origin of both subaging and end of aging behavior in glassy dynamics. The mechanism combines real and configuration space properties of the state produced by the initial thermal quench which initiates the aging process.


Effects of hypoxia on the circadian patterns in men.
We tested the hypothesis that acute hypoxia may alter the circadian pattern of body temperature in adult humans. Six healthy subjects were studied in normoxia, hypoxia (approximately 13% inspired O(2)), and again normoxia, each session lasting >24 h and spaced a few days apart, with a constant routine protocol of sustained wakefulness and minimal activity. Some parameters (e.g., tympanic and abdominal temperatures, heart rate) were recorded continuously; others (e.g., oxygen consumption and pulmonary ventilation) were monitored for approximately 10 min every 2 h. The amplitudes of the circadian oscillation of tympanic, abdominal, and calf skin temperatures were reduced in hypoxia, averaging, respectively, 61%, 80% and 50% of the normoxic amplitude. Oxygen consumption and pulmonary ventilation, which presented a circadian pattern in normoxia, had no longer significant oscillations during hypoxia, whereas the opposite was the case for heart rate and diastolic pressure. Therefore, acute hypoxia can disturb the normal circadian patterns and, specifically, depress those of body temperature. These effects, qualitatively similar to those observed in chronically hypoxic animals and humans, could contribute to sleep disturbances at high altitude.


Polypeptide synthesis directed by DNA as a messenger in cell-free polypeptide synthesis by extreme thermophiles, Thermus thermophilus HB27 and Sulfolobus tokodaii strain 7.
Polypeptide synthesis at high temperature directed by single strand DNA as a messenger was investigated using cell-free extracts of an extremely thermophilic bacterium, Thermus thermophilus strain HB27, and a hyperthermophilic, acidophilic archaeon, Sulfolobus tokodaii strain 7. Aminoglycoside antibiotics enhanced the reaction; neomycin stimulated it most effectively when the extract of the thermophilic bacterium was used, and paromomycin was the best among the antibiotics tested for the extract of the hyperthermophilic archaeon. A common correlation was found between the stimulation of DNA-directed polypeptide synthesis and the misreading rate in RNA-directed polypeptide synthesis. Spermine stimulated the reaction directed by DNA like in the case of poly(Phe) synthesis directed by poly (rU). The cell-free systems can be used for direct production of proteins from genes in high throughput studies on the structural genomics of thermophilus.


Normalization of estradiol receptor kinetics and hormonal activity in uterus of streptozotocin-induced diabetic rats treated with insulin.
In response to ip 17 beta-estradiol injection, ovariectomized streptozotocin-induced diabetic rats showed a decreased early and late stimulation of uterine protein synthesis as compared to nondiabetic controls. An early nuclear loss of estradiol-receptor complex and an accelerated estradiol clearance from the circulating blood were also observed in these animals. To establish whether these alterations in hormone kinetics and activity were related to the diabetic state, further investigation was done by treating diabetic animals with insulin, during 18 consecutive days after 3 to 8 months of long standing diabetes (type I treatment) or during 10 weeks starting immediately at the onset of the streptozotocin-induced disease (type II treatment). Both types of treatment either restored (type I) or preserved (type II) a normal body weight, low glycemia, and absence of glycosuria. Both types of treatment also restored a normal hormonal clearance so that higher plasma levels of estradiol at 30 and 90 min were noted after ip injection when compared to untreated diabetics. Nuclear retention of the estradiol-receptor complex was significantly higher in treated diabetics at 210 min as compared to the nondiabetic controls. Finally, stimulation of early protein synthesis at 90 min was normalized after both types of treatment. From the above observations it is concluded that insulin treatment restored a normal estrogen metabolism in diabetics, resulting in a prolonged retention of the estradiol-receptor complex in the uterine nuclei; the latter event in turn elicited a normal hormonal activity on protein synthesis. A direct influence of the diabetic state and of insulin treatment on the receptor kinetics and/or on the tissue response to the hormonal stimulus may however not be excluded.


Large orbital moments and internal magnetic fields in lithium nitridoferrate(I).
The iron nitridometalates Li2[(Li(1-x)Fe(I)(x))N] display ferromagnetic ordering and spin freezing. Large magnetic moments up to 5.0mu(B)/Fe are found in the magnetization. In Mössbauer effect studies huge hyperfine magnetic fields up to 696 kOe are observed at specific Fe sites. These extraordinary fields and moments originate in an unusual ligand field splitting for those Fe species leading [within local spin density approximation (LSDA)] to a localized orbitally degenerate doublet. Including spin-orbit interaction and strong intra-atomic electron correlation (LDA+SO+U) gives rise to a large orbital momentum.


Anhydrolide macrolides. 1. Synthesis and antibacterial activity of 2,3-anhydro-6-O-methyl 11,12-carbamate erythromycin A analogues.
A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-susceptible Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, as well as improved activity compared to erythromycin A against the inducibly MLS (macrolide, lincosamide, and streptogramin B)-resistant organisms. Structure-activity studies revealed that arylalkyl carbamates with two and four carbon atoms between the aromatic moiety and carbamate nitrogen have the best in vitro activity. All of the C-10 epi analogues evaluated were found to have substantially less activity than the corresponding natural C-10 isomer. Several analogues demonstrated moderate antibacterial activity against the constitutively resistant S.aureus A-5278, S. pneumoniae5979, and S.pyogenes 930. However, despite potent in vitro activity, these analogues showed only moderate in vivo activity in mouse protection studies.


Measurement and treatment of radiographic progression in ankylosing spondylitis: lessons learned from observational studies and clinical trials.
One of the major goals of treatment of ankylosing spondylitis is to prevent or slow the development of spinal new bone formation. Recent observational studies are compared with the results from clinical trials for the effects of tumor necrosis factor-alpha inhibitors (TNFi) and NSAIDs on radiographic measures of spinal damage. Data from clinical trials indicate that treatment up to 2 years with TNFi was not associated with a difference in rates of progression of spinal damage, compared with historical controls. These studies were based on open-label extensions, and analyzed as cohort studies. Recent observational studies have suggested that TNFi may reduce radiographic progression. The different conclusions may be related to the longer treatment and observation period of these observational studies, which may have permitted detection of changes in this slowly evolving process. There is emerging evidence from a clinical trial and retrospective studies that continuous NSAID use may slow radiographic progression. Lack of evidence that TNFi slows radiographic progression in ankylosing spondylitis in data from clinical trials may be because of the design of these studies, and possibly not a true null treatment effect.


Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy.
Sorafenib is used worldwide as a first-line standard systemic agent for advanced hepatocellular carcinoma (HCC) on the basis of the results of two large-scale Phase III trials. Conversely, hepatic arterial infusion chemotherapy (HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC, several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib, whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization, good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally, sorafenib is generally used to treat patients with Child-Pugh A, while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings, we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A, while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.


The relationship between the polymorphism of SG13S114 A/T in ALOX5AP gene and the vulnerability of carotid atherosclerosis in Chinese Han population.
The purpose of this study was to determine the relationship between the polymorphism of SG13S114 A/T in ALOX5AP gene and the vulnerability of carotid atherosclerosis in Chinese Han population. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) of SG13S114 A/T in ALOX5AP gene was performed for 284 patients with atherothrombotic cerebral infarction, of which 152 cases were diagnosed with stable plaque and the other 132 cases had vulnerable plaques. We found that the frequency of SG13S114 AA genotype and A allele of ALOX5AP gene in the cases with vulnerable plaques was significantly higher than those in the cases with stable plaques. These results suggested that high expression of SG13S114 AA genotype was related to the vulnerability of carotid atherosclerosis. SG13S114 A allele may be a risk factor of vulnerable plaques.


Monitoring of interaction products of cis-diamminedichloroplatinum(II) and cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) with DNA in cells from platinum-treated cancer patients.
The formation and stability of interaction products between the anti-cancer drug cis-diamminedichloroplatinum(II) (cis-DDP) and DNA were studied in buccal epithelial and urinary cells from ten cancer patients who received cis-DDP-based therapy. Buccal cells were collected 1 h before and 1-2 h after i.v. infusions with cis-DDP. The interaction products were visualized in an immunocytochemical peroxidase assay, using an antiserum against cis-DDP-modified calf thymus DNA. The nuclear staining density was measured by microdensitometry. Nuclear staining densities in buccal cells after infusions of greater than or equal to 20 mg/m2 cis-DDP were always higher than pretreatment values. Repeated sampling from individual patients treated for 2-5 consecutive days with daily doses of 20-70 mg/m2 cis-DDP indicated that cis-DDP-DNA binding in buccal cells increased in proportion to the cumulative total dose of cis-DDP. The variation in dose-density response between patients was 17%. Apparent adduct loss in buccal cells from four patients, as measured 8-17 days after the last infusion, amounted to 67-86%. Platinum-induced DNA modifications could also be detected in buccal cells from two cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)-treated patients. In vitro experiments with human buccal cells and lymphocytes indicated linear relationships between DNA modification and either cis-DDP concentration or incubation time. Nuclear staining densities in pretreatment buccal cells from ten cancer patients treated in vitro with 33 microM cis-DDP for 1 h revealed that interpatient variation in in vitro DNA modification by cis-DDP was low. No quantitative correlation was found between in situ and in vitro DNA modification.


20-Day Trend of Serum Potassium Changes in Bam Earthquake Victims with Crush Syndrome; a Cross-sectional Study.
Many of those who survive following an earthquake die in the next phase due to preventable and treatable medical conditions such as hyperkalemia. The present study aimed to evaluate the trend of potassium changes in crush syndrome patients of Bam earthquake. In this retrospective cross-sectional study, using the database of Bam earthquake victims, which were developed by Iranian Society of Nephrology following Bam earthquake, Iran, 2003, the 20-day trend of potassium changes in > 15 years old crush syndrome patients was evaluated. 135 crush syndrome patients with the mean age of 29.9 ± 9.91 years were evaluated (56.3% male). Mean potassium concentration during the first 3 days of admission was 5.6 ± 1.3 mEq/L. On the day of admission, 43.1% (95% CI: 34.0 - 52.2) had normal potassium concentration, 3.4% (95% CI: 0.1 - 6.8) had hypokalemia, and 53.4% (44.3 - 62.6) had hyperkalemia. During 20-day follow-up, 62.3% (95% CI: 66.7-71.9) of the patients had normal potassium. While, 11.5% (95% CI: 9.7-13.3) had hypokalemia and 19.2% (95% CI: 17.0-21.5) had hyperkalemia. As the days of hospitalization increased, prevalence of hyperkalemia decreased while hypokalemia increased. On the 17th day 21.2% (95% CI: 2.2-39.9) had hypokalemia and 10.5% (95% CI: 0.1 - 24.7) had hyperkalemia. Findings of the present study showed that following urine alkalinization and fluid resuscitation, the prevalence of hyperkalemia reduced, but hypokalemia developed. It seems that the correction of serum potassium level should be accompanied by precise monitoring of intake and output of the patient and prescription of reasonable amount of intravenous fluid.


Bile salts, hypotension and obstructive jaundice.
We have examined the effects of bile duct ligation on vascular and extravascular smooth muscle responsiveness to noradrenaline and tyramine using isolated rat hindlimb perfusion, and portal vein and vas deferens preparations. Bile duct ligation reduced the contractile responses to noradrenaline of vascular and extravascular smooth muscle. Exposure of smooth muscle to some bile salts caused a reduction in contractility. This effect was dependent upon bile salt type and concentration. These studies in vitro suggest that the reduced total peripheral resistance and hypotension seen in obstructive jaundice cannot be explained by a spasmolytic effect of some of the bile salts on smooth muscle.


Factors predictive of Ponseti casting for treating clubfoot: analysis of Bayesian Poisson regression model.
Clubfoot is a growing public health concern in Bangladesh, with the incidence of approximately 0.64 to 6.8 in every 1000 live births. For over a decade, Ponseti method has been considered a gold standard for treating the clubfoot. Despite few studies have been estimating the number of casts required to correct the clubfoot deformities by Ponseti method, the subject of interest has always remained. Therefore, this current study aimed to investigate the significant predictive factors for the number of casts required to correct congenital clubfoot. In this retrospective cohort study, we used Bayesian Poisson Regression Model to investigate the influencing factors that could predict how many casts are needed to correct the clubfoot. We included 69 patients with 99 affected feet, who completed their corrective phase of treatment in the Ponseti method. For this cohort study, we integrated only pre-tenotomy casting data with no age restrictions. We used Bayesian Poisson regression analysis technique to estimate the predictive factors. In Bayesian Poisson model, age was the most influencing predictive factor (24.3%) for increasing the number of castings to correct the clubfoot deformity. The clubfoot offspring of the ≤1-year-old was positive, and the incidence rate increased significantly with the casting number. The number of Ponseti casts in male clubfoot children was 28% higher than in female, and this was marginally statistically significant. There was no marked change estimated in the pattern of clubfoot, foot involvement and Pirani score of the severity. We concluded that the age factor may influence the number of casts required for the correction of clubfoot and specifically ≤ 1-year-old children are highly impacted. Treating clubfoot at an early age is suggested in this study to increase the success of clubfoot treatment and decrease the risk of relapse.


Effect of optimized thrombus aspiration on myocardial perfusion and prognosis in acute ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention.
To investigate the impact of optimized thrombus aspiration on myocardial perfusion, prognosis, and safety in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention(primary PCI). A total of 129 patients with STEMI were randomly allocated into control group (Subgroup A and B) and experimental group(Subgroup C and D). Control group received percutaneous transluminal coronary angioplasty (PTCA),thrombus aspiration and primary PCI. Experimental group received optimized thrombus aspiration and primary PCI. The number of thrombus aspiration was less than 4 times in Subgroup A and C. The number of thrombus aspiration was performed more than 4 times in Subgroups B and D. The classification of thrombi extracted, the TIMI flow grade, the incidence of no-reflow and slow flow, cTFC, TPI and CK-MB at 12 h and 24 h after stenting, ST segment resolution of ECG after stenting, NT-proBNP, LVEFat 24 h, 30 days and 180 days after stenting were compared between groups. The incidence of intraoperative and postoperative bleeding complications, stroke events and major cardiovascular events (MACE) were recorded and compared between groups. The classification of thrombi extracted in the experimental group was higher than that in the control group. The TIMI flow grade of the experimental group was better than the control group after thrombus aspiration. After stenting, the advantage still existed, but the difference was not statistically significant. On cTFC, the experimental group was lower than the control group, but the difference was not statistically significant; After stenting the experimental group was significantly lower than the control group. The CK-MB at 12 h and 24 h of the experimental group was lower than the control group. After thrombus aspiration the incidence of no-reflow in the experimental group was significantly lower than that in the control group; after stenting the incidence of no-reflow in the experimental group was still lower than the control group, but no statistically difference. After thrombus aspiration and stenting the incidence of slow flow in the experimental group were lower than that in the control group. After stenting, NT-proBNP at 24 h was lower in the experimental group than that in the control group, However, there was no statistical difference; after stenting, The NT-proBNP in the experimental group was lower than that in the control group at 30 days and 180 days. After stenting, LVEF of the experimental group was significantly higher than the control group at 24 h and 30 days; superiority remained after 180 days but no statistical difference. There was no statistical difference between two groups for intraoperative and postoperative bleeding complications, stroke events, and MACE events. In Subgroup analysis,there was no significant difference in the classification of thrombi extracted, TIMI flow grade, cTFC, CK-MB,NT-proBNP and LVEF between group C and D, but group A was better than group B. Analysis of variance showed that the optimal number of suction was 4-5 times. Optimized thrombus aspiration can significantly improve myocardial perfusion and short-term and medium-term prognosis of STEMI patients after PCI, and reduce the incidence of slow flow and no-reflow. The optimal suction times were 4-5 times. Traditional aspiration method with more aspiration times is harmful to cardiac prognosis. Thrombus aspiration does not increase the incidence of stroke events and is safe.Clinical Trial Registration: identifier, ChiCTR2300073410.


Speckle image reconstruction of the adaptive optics solar images.
Speckle image reconstruction, in which the speckle transfer function (STF) is modeled as annular distribution according to the angular dependence of adaptive optics (AO) compensation and the individual STF in each annulus is obtained by the corresponding Fried parameter calculated from the traditional spectral ratio method, is used to restore the solar images corrected by AO system in this paper. The reconstructions of the solar images acquired by a 37-element AO system validate this method and the image quality is improved evidently. Moreover, we found the photometric accuracy of the reconstruction is field dependent due to the influence of AO correction. With the increase of angular separation of the object from the AO lockpoint, the relative improvement becomes approximately more and more effective and tends to identical in the regions far away the central field of view. The simulation results show this phenomenon is mainly due to the disparity of the calculated STF from the real AO STF with the angular dependence.


CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.
Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis. We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays. We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.


Ebstein's anomaly of the left-sided atrioventricular (AV) valve in AV discordance.
Prosthetic valve replacement of the left-sided atrioventricular (AV) valve was performed in a patient with AV discordance and Ebstein's anomaly of the left-sided AV valve without other associated anomalies. An anatomical study of 22 specimens with AV discordance did not show a case with similar anatomy; 5 hearts had mild degrees of downward displacement of the attachment of the left-sided AV valve leaflets, with marked dysplastic changes and variable degrees of hypoplasia. The surgical implications are different according to the degree of downward displacement of the leaflets. This feature and the size of the annulus and the morphologically right ventricle should be considered in preoperative evaluation, along with the operative approach, possible presence of atrialization of the wall of the proximal chamber and the relation of the left AV valve to the conduction system. Preoperative diagnosis of the anomaly is possible by angiocardiography and other methods.


Terbinafine levels in serum, stratum corneum, dermis-epidermis (without stratum corneum), hair, sebum and eccrine sweat.
We determined terbinafine levels in serum, stratum corneum, dermis-epidermis (without stratum corneum), hair, sebum and eccrine sweat before, during and after 250 mg doses orally to volunteers once daily. Terbinafine is concentrated rapidly in stratum corneum (up to 9.1 micrograms/g of tissue) primarily by diffusion from the vascular system through the dermisepidermis. It also reaches high concentration in sebum (up to 45.1 micrograms/ml) after several days and continue to concentrate in sebum for up to two days after discontinuation of drug. Hair concentration reach levels of 2.6 micrograms/g of tissue indicating high drug levels in and around the hair follicle. It is not found in sweat. Plasma levels range between 0.1 and 1.0 micrograms/ml. There is a tenfold accumulation of drug in stratum corneum by day 2. Elimination of drug from tissue occurs with a half-life of 4 to 5 days and with the potential for drug levels above fungicidal concentrations for dermatophytes for more than 3 weeks. The tissue pharmacokinetic profile of terbinafine is similar to that of another lipophilic drug, itraconazole, but is very different from ketoconazole and griseofulvin. Higher levels of terbinafine are achieved than of either of the imidazoles and remain longer than griseofulvin.


A new science of happiness: the paradox of pleasure.
The pursuit of happiness is enshrined in the founding document of our nation as a fundamental and inalienable right. Yet nowhere is the method of this pursuit clearly defined. What, exactly, does it mean to be happy, and how can such happiness be sustained over the long term? Can happiness be accurately gauged or measured? How does the paradoxical relationship between happiness and pleasure shape our quest to lead the good life? And what does modern science have to tell us about this universal yet elusive pursuit? Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included attorney and author Kim Azzarelli, historian Darrin McMahon, and social psychologist Barry Schwartz, who joined forces to share their research and insight on happiness, pleasure, and the coveted good life.


Childhood obesity.
Childhood obesity has assumed epidemic proportions and it is currently one of the most prevalent public health problems. The pathophysiology of excess weight gain is complex with interactions between genetic factors, environment and biological factors. In this review, we highlight the epidemiology of childhood obesity and discuss clinical evaluation of a child with obesity. A staged approach to treatment is detailed. We discuss the role of lifestyle modifications, pharmacotherapy and bariatric surgery as treatment strategies.